title: Combination of budesonide/formoterol on demand improves asthma control by reducing exercise-induced bronchoconstriction.
abstract: BACKGROUND
  In mild asthma exercise-induced bronchoconstriction (EIB) is usually treated with inhaled short-acting β2 agonists (SABAs) on demand.
  
  
  OBJECTIVE
  The hypothesis was that a combination of budesonide and formoterol on demand diminishes EIB equally to regular inhalation of budesonide and is more effective than terbutaline inhaled on demand.
  
  
  METHODS
  Sixty-six patients with asthma (>12 years of age) with verified EIB were randomised to terbutaline (0.5 mg) on demand, regular budesonide (400 μg) and terbutaline (0.5 mg) on demand, or a combination of budesonide (200 μg)  + formoterol (6 μg) on demand in a 6-week, double-blind, parallel-group study (ClinicalTrials.gov identifier: NCT00989833). The patients were instructed to perform three to four working sessions per week. The main outcome was EIB 24 h after the last dosing of study medication.
  
  
  RESULTS
  After 6 weeks of treatment with regular budesonide or budesonide+formoterol on demand the maximum post-exercise forced expiratory volume in 1 s fall, 24 h after the last medication, was 6.6% (mean; 95% CI -10.3 to -3.0) and 5.4% (-8.9 to -1.8) smaller, respectively. This effect was superior to inhalation of terbutaline on demand (+1.5%; -2.1 to +5.1). The total budesonide dose was approximately 2.5 times lower in the budesonide+formoterol group than in the regular budesonide group. The need for extra medication was similar in the three groups.
  
  
  CONCLUSIONS
  The combination of budesonide and formoterol on demand improves asthma control by reducing EIB in the same order of magnitude as regular budesonide treatment despite a substantially lower total steroid dose. Both these treatments were superior to terbutaline on demand, which did not alter the bronchial response to exercise. The results question the recommendation of prescribing SABAs as the only treatment for EIB in mild asthma.
authors.affiliation: Division of Respiratory Medicine and Allergy, Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, , Stockholm, Sweden.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Lazarinis
authors.forename: Leif
authors.initials: L
authors.lastname: Jørgensen
authors.forename: Tommy
authors.initials: T
authors.lastname: Ekström
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.forename: Barbro
authors.initials: B
authors.lastname: Dahlén
authors.forename: Teet
authors.initials: T
authors.lastname: Pullerits
authors.forename: Gunilla
authors.initials: G
authors.lastname: Hedlin
authors.forename: Kai-Håkon
authors.initials: KH
authors.lastname: Carlsen
authors.forename: Kjell
authors.initials: K
authors.lastname: Larsson
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D001250:Asthma, Exercise-Induced / Q000503:physiopathology / Q000517:prevention & control*; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005080:Exercise Test / Q000379:methods; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D013726:Terbutaline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014797:Vital Capacity / Q000187:drug effects; D055815:Young Adult
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D005938:Glucocorticoids; D019819:Budesonide; D013726:Terbutaline; D000068759:Formoterol Fumarate
keywords: Asthma; Exercise